We have successfully fabricated apatite-fiber scaffolds (AFSs) that enable three-dimensional cell culture. The AFSs possessing large pores of 100~250 μm and micro pores of about 5 μm were fabricated by firing the green compacts consisting of the single-crystal apatite fibers and the carbon beads with a size of 150 μm. In order to enhance the mechanical properties of the AFSs, we have improved the process of AFS fabrication: Collagen gel (type I) solutions were introduced into the pores in the scaffolds; in addition, the resulting apatite/collagen scaffolds were chemically modified by thermally dehydrated cross-linking. Actually, the results of compressive strength tests show that the value of the AFS with chemically cross-linked I-collagen was about twice as high as that of the conventional AFS without I-collagen. We conclude that combination of I-collagen and thermal dehydrated cross-linking is effective for enhancement of the mechanical properties of AFSs.